Targeted antifungal delivery system: β-Glucosidase sensitive nystatin-star poly(ethylene glycol) conjugate

A new targeted intravenous conjugate of nystatin with pentaerythritol poly(ethylene glycol)ether has been prepared and characterised (NY4-sPEG, M= 25 160). The conjugate contains a beta-D-glucopyranoside molecular switch sensitive to beta-glucosidases (E.C.3.2.1.21), which are specifically present in the enzyme outfit of fungal pathogens. The investigated conjugate is stable under in vitro conditions for 24h (solution of phosphate buffer pH = 7.4). Spectrophotometrically controlled releasing of nystatin in model medium containing beta-glucosidase ((Aspergillus niger) 2 mg/ml., 66.6 units/g; pH 7.4,2 x 10(-2) M), reported decomposition half-life of conjugate T-1/2 = (88 +/- 2) s. This implies that releasing of nystatin is controlled only enzymatically. (C) 2009 Elsevier B.V. All rights reserved.